The hidden island of addiction: the insula

“The insula has been implicated in habit circuitry and is believed to mediate cue-induced urges [50], with the anterior insula also thought to translate interoceptive signals into self-awareness of subjective feelings and perhaps playing more of a role in decision-making processes [51, 52].”

“…study, the effects of the reflective and impulsive factors remained significant, but temptation did not exert a direct effect on system use; which is aligned with the neuro-scientific evidence regarding the role of insular activity in decision making (Naqvi et al., 2007; Naqvi and Bechara, 2009, 2010).”

“…system are influenced by interoceptive processes mediated by the insula include imaging studies illustrating activity within the insula correlating with subjects' ratings of urge for cigarettes, cocaine, alcohol, and heroin (Craig, 2009; Naqvi and Bechara, 2009; Verdejo-Garcia et al., 2012).”

“So it is not surprising that many neuroimaging studies have found increased activation of the IC in subjects exposed to drug related stimuli, and that IC activation was correlated with conscious experience of the urge to take drugs (Naqvi and Bechara, 2009).”

“In addition, it has been published that lesion of the insular cortex leads to recovery of nicotine addiction (38), suggesting that the insula is a key brain structure implicated in (food) cravingreward, processing, and modulation of hedonic response, beyond food sensory stimuli integration.”

“investigations have demonstrated that 1) cigarette smoking or varenicline treatment dampens abstinence-induced elevated activity within the amygdala (4,55,56), and 2) drug cues and smoking urges increase activity within the insula (6), the functional interface between these regions has heretofore been unexplored durin…”

“The correlations with insula are interesting in light of several studies implicating the role of the insula in substance abuse (Naqvi and Bechara, 2009; Naqvi et al., 2007) and recent studies showing that the anterior insula is important for intertemporal choices when a delay condition is present (Luhmann et al.”

“The insula has been hypothesized to have a significant role in interoception awareness, and thus may have a casual role in maintaining addiction to nicotine through its representation of negative bodily experiences associated with withdrawal and craving (Naqvi and Bechara, 2009).”

“Moreover, additional reports have shown that interoceptive signals within the insula (Craig, 2002; Gray & Critchley, 2007) are associated with cue-induced urges that result in experiences of “craving” (Naqvi & Bechara, 2009; Naqvi, Rudrauf, Damasio, & Bechara, 2007; Verdejo-García & Bechara, 2009).”

“Recent work also points that somatosensory signaling in the insula may contribute significantly to addiction, particularly with urges to consume the drug of abuse (30).”

“The question becomes: What might the common role of the insula be across the different tasks used in these previous studies? Increasing evidence points to the important role of the insula in translating interoceptive signals into urges (eg, Craig, 2009 ; Naqvi & Bechara, 2009 ).”

“Given its involvement in awareness of subjective states, along with reports of damage to this region reducing craving in cigarette smokers (Naqvi et al, 2007) and its activation associated with drug craving (Bonson et al, 2002; Brody et al, 2002; Filbey et al, 2009), the insula has been highlighted as having an import…”

“Interestingly, a key component of the network where sensitized activation is seen is the insula, a brain region that encodes negative interoceptive states, and whose anterior part has a high degree of reciprocal connectivity with the amygdala complex (Naqvi and Bechara, 2009).”

“This happens because the translating of somatic signals into subjective experience of craving increases sensitivity toward addiction-related cues and can reduce inhibition resources availability (118, 120).”

“The insula is known to play a crucial part in addiction because of its role in conscious urges to abuse drugs.(27) Functional imaging studies have shown activation of the insula during urges for cigarette smoking,(2830) cocaine,(3132) and alcohol,(3334) and insular activity has frequently been correlated with self-rep…”

“…the perception of pain (Bornhovd et al., 2002); and there is also evidence that this structure has a role in the maintenance of drug addiction (Naqvi and Bechara, 2009; Garavan, 2010), as well as more general evidence for its involvement in a myriad different tasks involving emotional…”

“It represents internal bodily needs (e.g., hunger, pain, fatigue, drug craving), monitors their satisfaction/frustration (e.g., satiation, deprivation), and integrates the bodily information into subjective feelings (Goldstein et al., 2009; Naqvi & Bechara, 2009).”

“The interaction of ventral striatum with the right insula was negative during aversive and positive during rewarding events, possibly reflecting interoceptive visceral states (Critchley et al. 2004; Naqvi and Bechara 2009) triggered by the game events; consistently, anatomical connections have been demonstrated betwee…”

“…(Gallagher et al., 1999), including drugs of abuse (Volkow & Fowler, 2000; Fuchs et al., 2004; Contreras et al., 2007; Wang et al., 2007), and recent results show a strong association of insular cortex activation and abstinence-induced cravings to smoke (for review see Naqvi & Bechara, 2009).”

“This accords with lesion and imaging studies which implicate the anterior insula in subjective drug craving (63).”

“The insula plays an important role in the craving of addictive behaviours and it might also facilitate withdrawal symptoms by translating the physiological state of withdrawal into dysphonia [41].”

“…in mediating the near-miss effect is consistent with its involvement in mediating subjective craving in response to drug (Garavan et al., 2000; Naqvi and Bechara, 2008), food (Pelchat et al., 2004; Tang et al., 2012), and other addiction-related cues (Clark and Limbrick-Oldfield, 2013; Hommer…”

“The insula has currently attracted attention as an important brain region in addiction by representing conscious urges to the drug of abuse via connections with the ventromedial prefrontal cortex and the amygdala (Naqvi et al., 2007; Naqvi and Bechara 2009).”

“This paralimbic cortex is highly coupled with the anterior cingulate cortex and amygdala, which together are likely critical for integrating interoceptive information into emotion (Craig, 2002; Critchley et al., 2004; Naqvi and Bechara, 2009).”

“In accord with the neurocircuit model of addiction (Naqvi & Bechara 2009; Sutherland et al. 2012; Naqvi et al. 2014), we observed greater positive connectivity between the right anterior insula with ACC in IGDs, relative to HCs, in association with duration of Internet gaming in IGDs.”

“First, the insula was linked to substance addiction through studies on patients with insular brain lesions; among patients with this lesion who smoked, most reported marked decrease in cravings to use cigarettes and overall cigarette smoking (Naqvi and Bechara, 2009).”

“Within this framework, the presence of focal and bilateral deactivation in the insular cortex in the OX1R antagonist group is of great interest, given the central role of this structure as integrator of interoceptive states into conscious feelings and decision-making processes that precipitate relapse [38].”

“…evidence has suggested that poor inhibitory control resulting from sub-optimal functioning of prefrontal cortical structures (Volkow & Fowler, 2000; Naqvi & Bechara, 2009; Ersche et al., 2012) that may precede (Volkow & Fowler, 2000; Ersche et al., 2012), or be the result of, chronic exposure to…”

“deficits in behavioral inhibition, decision-making ability, and environmental monitoring (9), which rely largely on normal insular as well as orbital and inferior frontal gyri functioning (10,11).”

“This information is transmitted to the anterior cingulate cortex, dorsal lateral PFC, and likely also the IFG, that gate whether to maintain on-going behavior or disrupt it and engage in drug use (Naqvi and Bechara, 2009).”

“The insula has been implicated in integrating interoceptive states into conscious feelings, decision making, and empathy and pain recognition in others (Craig, 2009; Decety & Jackson, 2006; Naqvi & Bechara, 2009), and thus may be important in understanding empathy deficits seen in youth AB.”

“This is remarkable, considering the involvement of this particular region in addiction (Naqvi and Bechara, 2009), self-regulation and executive”

“The insula is a key neural structure for representing the interoceptive effects of drug use, which are associated with conscious cue-induced urges (reviewed by Naqvi and Bechara, 2009).”

“The insular cortex is involved in homeostatic and motivational control and has also recently been found to be critical in maintenance of addictions [Mizuhiki et al., 2012; Naqvi and Bechara, 2009; Small, 2010], whereas the orbitofrontal cortex links rewards to hedonic experience [Kringelbach, 2005].”

“…© 2012 Society for the Study of Addiction Addiction Biology, 18, 1013–1023 internal affective information into conscious experiences like craving (Naqvi & Bechara 2009), whereas the OFC involves reward evaluation and integrating affective information into the decision process (Koob & Volkow…”

“…disconnection of the IC from the NAc core on outcome devaluation First, we confirmed the connection between the IC and the NAc core (Allen et al., 1991; Wright and Groenewegen, 1996; Chikama et al., 1997; Reynolds and Zahm, 2005; Naqvi and Bechara, 2010, 2009) using retrograde tracing.”

“Both regions are constituents of the neurocircuitry maintaining addiction (Koob and Volkow 2010; Naqvi and Bechara 2009).”

“In all, task performance will be enhanced.”

“1; Naqvi & Bechara, 2009; Naqvi, Rudrauf, Damasio, & Bechara, 2007).”

“…toward immediate rewards by sensitizing the activity automatic emotional (amygdala) and incentive (ventral striatum) processes within the impulsive system, and by disabling prefrontal cortex regions necessary for reflective control processes (Naqvi & Bechara 2009, 2014; Verdejo-Garcia et al. 2012).”

“…with the anticipation or actual experience of receiving a reward (Kang et al. 2009), the insula seems to process a bodily desire for something rewarding without the surety of receiving the reward (Naqvi and Bechara 2009; Preuschoff, Quartz, and Bossaerts 2008; Vartanian, Mandel, and Duncan 2011).”

“…associated with urges and craving, and mediated through the insula, could further alter the dynamic balance between the automatic and regulatory control processes in a direction that facilitates automatic/implicit processing and hinders inhibitory control processing (e.g. see Naqvi & Bechara 2009).”

“Differentially greater activation was present in regions associated with cognitive deliberation and integration (dlPFC and PCC; Lee and Seo, 2007; Leech et al, 2012), mathematical calculations (angular gyrus; Zamarian et al, 2009), and motivational drive/ cravings (striatum and insula; Naqvi and Bechara, 2009; Shohamy…”

“Based on our baseline findings (GM volume in the anterior cerebellum larger in the CB than in the HC group, and negative correlations of cannabis exposure (gram per week) and cannabis related problems and GM volumes in the hippocampus and amygdala respectively within the CB group [17]) and on findings from previous st…”

“Consistent with a role in premonitory urges, the insula is also implicated in a variety of natural urges [57] and in urges in addiction [58].”

“We have referred to this neural system as the “reflective” system or prefrontal system [28]; and (3) based on more recent evidence on the effects of brain lesions on smoking behavior [40], we hypothesized that the strength of the two previously outlined neural systems can be modulated by the insula system involved in…”

“The insula is suggested to be a critical component of a decision-making network that integrates neuronal processing in PFC and limbic areas, and it putatively plays a key role in processing visceral drug urges (Naqvi et al. 2007; Naqvi & Bechara 2009).”

“Functional neuroimaging studies suggest that activity in the insula triggers the explicit motivation to use addictive drugs.(30) The VBM study results also correspond to those of previous studies showing that the PFC and insula contribute to the underlying mechanism of SUD.”

“This insular response may influence the balance between the impulsive and decision-making systems, thereby intensifying activity of the impulsive system and/or disabling the ability of the prefrontal cortex (PFC) to exert self-control (Naqvi & Bechara, 2009; Noel, Brevers, & Bechara, 2013).”

“during subjective drug urges (Naqvi and Bechara, 2009).”

“021 such as the vmPFC and AMYG have also been implicated in processing the reward value of various stimuli, including interoceptive stimuli (Naqvi and Bechara, 2009; Naqvi et al., 2007).”

“Damage to the insula has also been linked to deficits in decision making (51).”

“alterations were associated with an increased relapse propensity [41,42].”

“…al., 2000), dyspnea (Liotti et al., 2001), thirst (Denton et al., 1999; Egan et al., 2003), hypoglycemia (Teves et al., 2004), satiety and craving (Naqvi and Bechara, 2009) have substantiated activation in the insula, the ACC, and the PFC among other paradigm-specific cortical and subcortical…”

“These data support an important role for the insular cortex in drug addiction processes; for recent reviews see (Goldstein et al., 2009 and Naqvi and Bechara, 2009).”

“These include brain areas associated with processing and evaluating incentive salience, action execution, emotional arousal, interoception, intentionality, and planning (Rushworth et al., 2004; Moratti et al., 2008; Desmurget et al., 2009; Naqvi and Bechara, 2009).”

“…a prediction of the dynamic representation of interoceptive drug effects (such as the bitter taste or the local anesthesia induced by cocaine snorting) elicited by drug cues, which ultimately contributes partially to the conscious craving perception (Myrick et al., 2004; Naqvi and Bechara, 2009).”

“The insula is known to play a crucial part in addiction because of its role in conscious urges to abuse drugs [50].”

“Furthermore, the insula integrates interoceptive states into emotions and conscious feelings, and its reactivity has been suggested to serve as a biomarker to predict relapse in humans (Naqvi and Bechara, 2009; Janes et al., 2010).”

“The anterior insula has a strong connection with the amygdala (Naqvi and Bechara, 2009; MeyerLindenberg and Tost, 2012; Sescousse et al., 2013) and is involved in emotional processing and empathy (Vogt, 2005; de Vignemont and Singer, 2006; Fan et al.”

“Consistent with this view, the NAc-C receives strong projections from brain regions involved in incentive learning, such as the BLA and the IC (Wright and Groenewegen, 1996; Chikama et al., 1997; Sah et al., 2003; Naqvi and Bechara, 2009; Jones et al., 2010), indicating that it receives the information necessary to se…”

“Other brain regions such as the insula (involved in sensing physical or somatic states) and parietal cortex (involved in attentional processing) may also participate by influencing motivations and decisions to engage in addictive behaviors [76-78].”